遗传增强
脂质体
体内
基因传递
阳离子脂质体
转染
医学
病毒载体
作者
Zhen Ye,Mai Mohamed Abdelmoaty,Vishakha V. Ambardekar,Stephen M. Curran,Shetty Ravi Dyavar,Lora L. Arnold,Samuel M. Cohen,Devendra Kumar,Yazen Alnouti,Don W. Coulter,Rakesh K. Singh,Joseph A. Vetro
标识
DOI:10.1016/j.nano.2021.102363
摘要
Abstract RNA interference molecules have tremendous potential for cancer therapy but are limited by insufficient potency after i.v. administration. We previously found that Chol-DsiRNA polyplexes formed between cholesterol-modified dicer-substrate siRNA (Chol-DsiRNA) and the cationic diblock copolymer PLL[30]-PEG[5K] greatly increase the activity of Chol-DsiRNA against a stably expressed reporter mRNA in primary murine syngeneic breast tumors after daily i.v. dosing. Here, we provide a more thorough preliminary preclinical study of Chol-DsiRNA polyplexes against the therapeutically relevant target protein, STAT3. We found that Chol-DsiSTAT3 polyplexes greatly increase plasma exposure, distribution, potency, and therapeutic activity of Chol-DsiSTAT3 in primary murine syngeneic 4T1 breast tumors after i.v. administration. Furthermore, inactive Chol-DsiCTRL polyplexes are well tolerated by healthy female BALB/c mice after chronic i.v. administration at 50 mg Chol-DsiCTRL/kg over 28 days. Thus, Chol-DsiRNA polyplexes may be a good candidate for Phase I clinical trials to improve the treatment of breast cancer and other solid tumors.
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